Analytical Research and Development, Merck & Co., Inc., Rahway, NJ, 07065, United States.
Analytical Research and Development, Merck & Co., Inc., Rahway, NJ, 07065, United States; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, IN, 47907, United States; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, United States; Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT, 06269, United States.
Solid State Nucl Magn Reson. 2022 Aug;120:101796. doi: 10.1016/j.ssnmr.2022.101796. Epub 2022 May 25.
Solid-state NMR has been increasingly recognized as a high-resolution and versatile spectroscopic tool to characterize drug substances and products. However, the analysis of pharmaceutical materials is often carried out at natural isotopic abundance and a relatively low drug loading in multi-component systems and therefore suffers from challenges of low sensitivity. The fact that fluorinated therapeutics are well represented in pipeline drugs and commercial products offers an excellent opportunity to utilize fluorine as a molecular probe for pharmaceutical analysis. We aim to review recent advancements of F magic angle spinning NMR methods in modern drug research and development. Applications to polymorph screening at the micromolar level, structural elucidation, and investigation of molecular interactions at the Ångström to submicron resolution in drug delivery, stability, and quality will be discussed.
固态 NMR 已逐渐被公认为一种高分辨率、多功能的光谱技术，可用于对药物物质和产品进行表征。然而，药物材料的分析通常在自然丰度和相对较低的药物载量下进行于多组分体系中，因此存在灵敏度低的挑战。含氟治疗药物在药物研发中占有很大的比例，这为利用氟作为药物分析的分子探针提供了极好的机会。我们旨在综述 F 魔角旋转 NMR 方法在现代药物研究与开发中的最新进展。将讨论其在药物输送、稳定性和质量研究中对微摩尔级别的多晶型筛选、结构解析以及在埃至亚微米分辨率下的分子相互作用的应用。
